The recently reorganized Duke Comprehensive Cancer Institute (DCCI) is charged to serve as the center of all Duke activities in cancer, with an imperative to oversee all of the Duke cancer operations in the future. As a matrix center in one of the largest biomedical research institutes, the DCCI has been continuously supported by the National Cancer Institute (NCI) for over 36 years, by leveraging Duke's basic research strengths with significant clinical oncology research excellence which is enabled by treating 5,581 new cancer patients annually, enrolling over 1,000 patients annually onto therapeutic clinical trials, and enhanced by the presence of national oncology research resources, such as the data and statistical centers of two NCI-funded cooperative groups. Total membership in the DCCI is 285 members, with members having an increasingly prominent focus in cancer research and increased amount of NCI funding since 2004. Total funding for program members is $331,617,013, of which $269,525,804 is from peer-reviewed sources. A cancer focus is illustrated by $77,785,582 or 23.5% of funding from the NCI, the American Cancer Society or the Department of Defense. From 2004-2008, program members published 6,941 papers in peer-reviewed journals cited in PubMed. Of these publications, 10% are the result of intra-programmatic collaborations and 19% due to inter-programmatic collaborations. In this competitive renewal application, we request support our membership in 11 Research Programs supported by 17 Shared Resources. DCCI members made significant scientific advances including: the development of innovative genomic tests to predict which cancer patients would respond to specific chemotherapy, and basic insight into critical signaling pathways in cancer and developmental biology. The DCCI oversees all cancer related philanthropy at Duke, and these funds have been used to support recruitment of new members, innovative pilot projects, support of multidisciplinary research, and new laboratory and administrative space. This application for ongoing support of the DCC articulates the principles, goals and strategies for propelling the DCCI to fully leverage the enormous advances in biomedical research at Duke and beyond, to improve and extend the lives of cancer patients with cancer and at risk for cancer, and delivering these to society.